Novel prime-boost combinations of PSMA-based vaccines for prostate cancer

2572 Background and Methods The development of vaccination strategies targeted to tumor antigens holds great promise for cancer therapy. Prostate-specific membrane antigen (PSMA) is an attractive candidate self-antigen for vaccination based on its expression signature. PSMA is abundantly expressed on the surface of prostate cancer cells and on the neovasculature of a wide array of other tumors, but PSMA has limited expression in normal extraprostatic tissues. In prostate cancer, PSMA expression increases with disease progression, becoming highest in high-grade, metastatic, hormone-refractory disease. Our main goals are to overcome tolerance to PSMA by active immunization and to induce recognition and rejection of tumor cells expressing PSMA. We are investigating non-replicating vaccine replicon particles (VRP) based on the alphavirus, Venezuelan equine encephalitis virus. VRP have demonstrated potency in animal models, and infect cells in the lymph nodes where the replicon drives production of large quant...